Implantation of dedifferentiated fat cells ameliorates habu snake venom-induced chronic renal dysfunction in tenascin-C-deficient mice.

BACKGROUND/AIMS: We established dedifferentiated fat (DFAT) cells from mature adipocytes that differentiate to multiple lineages and have characteristics similar to those of mesenchymal stem cells. In this study, we evaluated the effect of implantation of DFAT cells on habu snake venom (HSV)-induced renal dysfunction in tenascin-C knockout (TC-KO) mice.

METHODS

Cultured DFAT cells were incubated with PDGF-BB and immunostained with anti-desmin antibody to determine mesenchymal differentiation. HSV was injected, and DFAT cells from GFP mice were implanted in TC-KO mice via the tail vein. Expression of tenascin-C, transforming growth factor-beta(1) (TGF-beta1), and fibronectin mRNAs in the renal cortex were evaluated by RT-PCR analysis.

RESULTS

Cultured DFAT cells showed desmin immunostaining in response to PDGF-BB.HSV injection induced glomerulosclerosis, which was significantly improved by implantation of DFAT cells. Serum BUN increased after HSV injection and was significantly decreased by implantation of DFAT cells. Tenascin-C mRNA was detected in the renal cortex in implanted mice. Expression of TGF-beta1 and fibronectin mRNAs increased in the renal cortex after HSV injection, and was significantly decreased by implantation of DFAT cells.

CONCLUSION

DFAT cells may provide a source for cell therapy for severe progressive renal disease.